Vaccine-induced immunity requires an intact immune system for optimal response and development of protective immunity. Since there is now almost universal vaccination from infancy for prevention of tetanus and infections of pneumococcal origin, it follows that new immune system regulating therapies should be studied for their effect on the ability to mount a productive antibody response to these vaccines. Depending on the type of vaccines administered, the antibody response generated is considered to be either relatively T-cell dependent or T-cell independent. Vaccines, such as tetanus toxoid, elicit a humoral response that is influenced by T cells and is considered T-cell dependent. Other vaccines, like pneumococcal vaccines, do not require T cells to induce an antibody response and are considered T-cell independent. However, T cells do contribute to the intensity of the antibody response and thus this response cannot be considered completely T-cell independent.
T-cell independent antigens (e.g. 23-valent pneumococcal vaccine) are typically polysaccharide in origin and can bind directly to receptors on the surface of B cells, thereby eliciting B cell differentiation and proliferation without an absolute requirement for T cell help. This applies to both primary and secondary responses to polysaccharide antigens. The 23-valent pneumococcal vaccine is recommended for patients at risk for developing pneumococcal infections (such as patients with sickle cell anemia, diabetes mellitus, chronic cardiovascular or pulmonary disorders, immunocompromised patients, and all adults over the age of 65 years).
Measurement of specific antibody production in response to a vaccine is a means of evaluating B cell function and helper T cell function. The antibody response to an antigen involves the presentation of the antigen via an antigen-presenting cell (APC) to helper T cells. These T cells then interact with B cells via the B cell receptor (cell surface IgM/IgG specific for the antigen) and “second signal” receptor ligand pairs to induce B cell activation and proliferation resulting in specific antibody production. Specific antibody production following vaccinations is measured at the pre-vaccine and post-vaccine serum antibody levels. The post-vaccine antibody levels are typically obtained 2-4 weeks after vaccination
Treatment with CTLA4Ig has been shown to improve the signs and symptoms of rheumatoid arthritis (RA). This has been shown in patients with active RA who have had an inadequate responses to methotrexate and also in patients with inadequate responses to anti-tumor necrosis factor therapy. CTLA4Ig treats RA by selectively modulating the CD80/CD86: CD28 costimulatory signal required for T-cell (T-lymphocyte) activation. This selective co-stimulation modulator inhibits T-cell activation by binding to CD80 and CD86, thereby blocking a costimulatory signal necessary for full activation of T cells, implicated in the pathogenesis of RA.
Timing of vaccine administration in relation to illnesses, other vaccines, and certain medications is recognized as important to the appropriate use of vaccines. With agents such as soluble CTLA4 molecules that affect T-cell activation, the timing of vaccine administration (pre-/post-CTLA4 dose) may affect the magnitude of the immune response. The effect of soluble CTLA4 molecules on response to therapeutic vaccines has not been previously evaluated.